富马酸二甲酯通过提高甲状腺功能减退症大鼠海马脑源性神经营养因子水平改善认知障碍。

Dimethyl fumarate improves cognitive impairment by enhancing hippocampal brain-derived neurotrophic factor levels in hypothyroid rats.

机构信息

Department of Endocrinology, The Third Affiliated Hospital of Zhejiang Chinese Medicine University, Hangzhou, 310000, China.

Departments of Psychiatry, Affiliated Mental Health Center, Zhejiang University School of Medicine, Hangzhou, 310000, China.

出版信息

BMC Endocr Disord. 2022 Jul 22;22(1):188. doi: 10.1186/s12902-022-01086-4.

BACKGROUND

Dimethyl fumarate (DMF) is an effective drug for multiple sclerosis and can improve the cognitive dysfunction caused by streptozotocin, but the effect on cognitive dysfunction caused by hypothyroidism is unclear.

METHODS

After the hypothyroidism rat model induced by propylthiouracil, we gave rats 25 mg/kg DMF by gavage. The body weight during model building and administration was recorded. The levels of T4 and T3 in serum were detected by an automatic biochemical analyzer. Morris water maze test was used to detect the effect of DMF on cognitive learning ability. The effect of DMF on Nissl bodies in the brain tissue was evaluated by Nissl staining. The mRNA and protein levels of BDNF in brain tissue were detected by quantitative reverse transcription-polymerase chain reaction and Western blot. The degrees of p-AKT/AKT and p-CREB/CREB in brain tissue were detected by Western blot.

RESULTS

After DMF treatment, the body weight of hypothyroid rats recovered, and the levels of T3 and T4 in the serum were ameliorated. DMF also reduced the escape latency and distance traveled, and increased the swim speed. The number of Nissl bodies and expression of BDNF, p-AKT/AKT, and p-CREB/CREB in the brain tissue were increased after DMF treatment.

CONCLUSION

DMF improved the cognitive dysfunction of hypothyroid rats by increasing the level of BDNF in the brain tissue of hypothyroid rats.

背景

富马酸二甲酯（DMF）是治疗多发性硬化症的有效药物，可改善链脲佐菌素引起的认知功能障碍，但对甲状腺功能减退引起的认知功能障碍的影响尚不清楚。

方法

用丙硫氧嘧啶诱导甲状腺功能减退大鼠模型后，给予大鼠 25mg/kg DMF 灌胃。记录模型制作和给药期间的体重。用自动生化分析仪检测血清中 T4 和 T3 的水平。用 Morris 水迷宫试验检测 DMF 对认知学习能力的影响。用尼氏染色评价 DMF 对脑组织尼氏体的影响。用定量逆转录聚合酶链反应和 Western blot 检测脑组织中 BDNF 的 mRNA 和蛋白水平。用 Western blot 检测脑组织中 p-AKT/AKT 和 p-CREB/CREB 的程度。